All visual information leaving the eye is conveyed in the activity of retinal ganglion cells (RGCs). In humans and other animals with a highly developed visual system, RGCs belong to functionally distinct classes that respond selectively to different features in the visual environment. The objective of the proposed research program is to determine the prenatal maturation of RGCs in the macaque monkey and the mechanisms that contribute to M and P cell differentiation. We will focus on the two major classes of primate RGCs, the M and P classes. The proposed study involves three sets of experiments. The first major series of experiments (Specific Aim 1) will test the hypothesis that RGCs are responsive to visual stimuli before birth and the differentiation of cells with M-like and P-like response properties begins before birth. The second series of experiments (Specific Aim 2) will test the hypothesis that M and P RGCs express class-specific differences in their intrinsic membrane properties and these differences emerge before birth. Finally, the third series of experiments will test the hypothesis that M and P RGCs express class-specific genes related to the development of distinct visual function, intrinsic physiological properties and morphological differences associated with these distinct visual pathways. The proposed research program will break new ground by increasing our understanding of the mechanisms underlying the formation of the M and P pathways which are a distinguishing feature of the primate visual system. Given the central importance of retinal ganglion cells for vision, it is important that we understand the mechanisms that guide their differentiation during development, as disorders during development underlie several illnesses affecting vision and visual processing. PUBLIC HEALTH RELEVANCE: Retinal ganglion cells provide the brain with information about the visual environment. Given the severe financial and quality-of-life consequences that follow from disorders of retinal ganglion cell function, it is important that we have a better understanding of the mechanisms that underlie their development. The goal of this proposal is to determine the cellular and molecular mechanisms that underlie the functional differentiation of retinal ganglion cells.